(a) Field of the Invention
The present invention relates to novel oxazolidinone derivatives having antibacterial activity, or a pharmaceutically acceptable salt thereof, a method for preparing the same, an antibacterial composition comprising the oxazolidinone derivative or a pharmaceutically acceptable salt thereof as an active ingredient, and a method for treating an infectious disease caused by pathogen using the same.
(b) Description of the Related Art
Since penicillin was discovered by Fleming at 1929, a lot of studies have been progressed on betalactam, aminoglucoside, macrolide, quinolone, tetracycline, glycopeptides antibiotics. When penicillin was first discovered by Fleming, it was called as a magical drug that can kill most bacteria. However, not long after the use, resistant bacteria was found from colon bacillus, and as strains having resistance to the antibiotics are continuously developed, resistant strains so-called super bacteria that does not respond to any antibiotics continuously appear.
Currently, more various kinds of antibiotics are developed, while resistance to the antibiotics is observed from various kinds of strains. As the application range of antibiotics is broadened, bacteria itself cause mutation more variously and thus resistance is increasing explosively. And, rapid increase of antibiotics raises resistance problem in a more complicated way than before. In practice, strains such as methicillin-resistant Staphylococcus Aureus (MRSA), methicillin-resistant Staphylococcus Epidermidis (MRSE), penicillin-resistant Streptococcus pneumonia, quinolone-resistant Staphylococcus Aureus (QRSA), vancomycin-resistant Staphylococcus Aureus (VRSA), vancomycin-resistant Enterococci (VRE), and multi-drug resistant Mycobacterium tuberculosis show resistance to most antibiotics in use. Thus, studies and developments of new antibiotics are required, and to overcome resistant strain problem, studies on antibiotics having new structure and mechanism of action are urgently demanded.
At 1987, Dupont company discovered that Dup-105 and Dup-721 having an oxazolidinone structure have antibacterial effects, and as results of researches on the pharmaceutical efficacy, disclosed that they have antibacterial activities against gram positive bacteria including resistant strains. Through studies on the structure-activity of the compounds of this type since then, at April, 2000, antibiotics of a new structure, i.e., a compound linezolid (Zyvox®) was developed by Pharmacia & Upjohn company 40 years after quinolone type antibiotics (WO 95/07271).
At 1997, it was known that Pharmacia's linezolid selectively binds to 50S ribosomal subunit adjacent to the interface of 30S ribosomal subunit (Antimicrob Agents Chemother 1997, 41:2132-2136), and the crystal structure wherein linezolid is binded to the 50S ribosomal subunit was reported (J. Med. Chem., 2008, 51, 3353-356). Although it is known that the oxazolidinone antibiotics manifests excellent pharmacokinetic property through new mechanism of action, which is different from those of the existing antibiotics, and is now in the position of a last resort to treat gram positive bacterial infection generated by MRSA or VRE, linezolid resistance is being reported among the gram positive bacteria.
Accordingly, there is a need for development of novel compounds having excellent efficacy against a broad range of antibiotics-resistant strains through modification of the chemical structure of oxazolidinone antibiotics.